There are millions of humans living with HIV/AIDS. Drugs and improved treatment regimens have successfully prolonged the lives of infected individuals. However, according to the CDC from 2008 through 2011, the annual estimated number and rate of diagnoses of HIV infection remained stable in the United States. Thus, there is a great need to develop a safe and effective HIV vaccine to reduce the spread of HIV infections.
Initial HIV vaccines candidates AIDSVAX BB and AIDSVAX B/E consisted of bivalent gp120 subunits of the viral envelope glycoprotein (Env). These vaccines elicited antibody responses in all of vaccinated participants but it was ineffective in preventing HIV-1 infection or in modifying postinfection markers of disease progression. The MRKAD5 vaccine is an adenovirus 5 (Ad5) vectored encoding Gag, Pol, and Nef. It elicited both HIV specific CD8+ and CD4+ T cell responses in most clinical trial participates but also failed to prevent infection. The ALVAC-HIV (vCP1521) vaccine contains a canary pox vector that encodes Gag, protease, and Env. ALVAC-HIV was studied in combination with AIDSVAX B/E boosts. This combination did not induce measurable CD8+ T cells in most clinical trial participants; however, it did induce antibody and CD4+ T cells and provided some protection against infection. See Rerks-Ngarm et al., N Engl J Med, 2009, 361:2209-2220 and Kintu et al., J Acquir Immune Defic Syndr. 2013, 63(1):1-8.
Veazey et al., report that the gastrointestinal tract is a major site of CD4+ T cell depletion and viral replication in SIV infection. Science, 1998, 280(5362):427-31. Brenchley et al., report that CD4+ T cell depletion occurs during all stages of HIV disease and occurs predominantly in the gastrointestinal tract. J Exp Med, 2004, 200(6):749-59. See also Li et al., Nature, 2005, 434(7037):1148-52 and Mattapallil et al., Nature, 2005, 434(7037):1093-7. Thus, there is a need for HIV vaccines and vaccination methods that protect the lymphoid system in the gastrointestinal tract.
Quigley et al. report a foreign protein incorporated on the tip of T3 pili in Lactococcus lactis (L. lactis) elicits systemic and mucosal immunity. Infect Immun. 2010, 78(3):1294-303. See also Bahey-El-Din & Gahan, Hum Vaccin, 2011, 7(1):106-9.
Xin et al. report orally administered recombinant L. lactis expressing surface-bound HIV Env. Blood, 2003, 102:223-8.